Vaccine Delivered Through Older Methods May Provide Better Immunity

7:51 January 19, 2010

Boston, MA – New research from Brigham and Women’s Hospital (BWH) shows that giving a vaccine through a scratch on the skin, a technique called scarification, results in a better immune response when compared to injecting the vaccine into the body, and that the amount of vaccine needed to generate the immune response through scarification is 100 times less. Nearly two centuries ago, the first vaccinations against smallpox were given via scarification. Today, virtually all modern vaccines are delivered by hypodermic needle and syringe.

Researchers also have found that the memory of the cells responsible for mounting an immune response may be more important than antibodies, which are generated from the types of needle and syringe vaccines most commonly used today. This cell memory resides in T cells, which are cells that are responsible for mounting an immune response to an invading virus, and are located not only in lymph nodes and blood but also in peripheral tissues, like skin and lung. These findings are published in a paper in Nature Medicine on January 17, 2010.

“This research illustrates the remarkable capacity of the most superficial layer of skin to generate powerful protective immune responses after vaccination, said Thomas Kupper, MD, senior researcher on the paper and chairman of the Department of Dermatology at BWH. “The ability of vaccination through injured epidermis-or scarification-to generate such powerful tissue resident protective T cells, is a completely novel observation that should make us reconsider the way we think about vaccine delivery for all infectious diseases, as well as cancer. After all, our immune system evolved over millions of years to respond to infections of injured skin, not vaccines delivered by hypodermic syringe into muscle.”

Lisa Liu, MD, PhD, lead author of the paper and physician in the Department of Dermatology at BWH, along with Kupper and colleagues designed a study to understand why scarification was so uniquely effective at generating immunity. They demonstrated that scarification with vaccinia virus – an infection induced by inoculation in order to confer resistance to smallpox – was vastly superior to delivery of the same vaccine by hypodermic needle and syringe, in the generation of robust immune responses. Researchers also tested a melanoma vaccine and found that the vaccine when delivered by scarification was vastly superior to vaccines delivered by multiple other injection routes in the protection against melanoma tumor growth in animals.

In further experiments, researchers mapped the immune response in the body following the delivery of vaccine by scarification. They found that when the virus enters the skin, viral particles are first filtered through lymph nodes before accessing the blood stream. In the lymph node is where researchers found two types of virus fighting T cells that were activated. The first population of T cells were designed to leave the lymph nodes to the blood stream and traffic to the skin – both the infected and normal skin. These early responder cells are rapidly able to destroy the virus in the skin and also remained in the skin for extended periods of time. Up to months later these cells were able to respond to and destroy a second skin infection. The second population of T cells also exited the lymph nodes to the blood stream, but from there they circulated to other lymph nodes in the body and remained indefinitely. Some of these cells also acquired the ability to travel to lung tissue, where they also remained for long periods of time. These cells were also able to be recruited to fight against a second infection many months after the original vaccine, whether the infection occurred in lung or skin.

“The lessons we are learning from these studies of vaccination by scarification could help us develop new and more powerful vaccines for influenza, HIV, malaria, and other infectious diseases,” said Kupper. “We should also continue to explore the implications for developing powerful cancer vaccines, like the one demonstrated by melanoma vaccine results in this study.”

This work was funded by the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health.

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